ArticleThe Biochemical journal2000
Interferons activate the p42/44 mitogen-activated protein kinase and JAK-STAT (Janus kinase-signal transducer and activator transcription factor) signalling pathways in hepatocytes: differential regulation by acute ethanol via a protein kinase C-dependent mechanism.
Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 67 citations in OpenAlex.
- Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus-Infected Liver Cells by Up-Regulating USP18.Alcoholism, clinical and experimental research · 2016Article
- IFNλ Stimulates MxA Production in Human Dermal Fibroblasts via a MAPK-Dependent STAT1-Independent Mechanism.The Journal of investigative dermatology · 2015Article
- Acetaldehyde accelerates HCV-induced impairment of innate immunity by suppressing methylation reactions in liver cells.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes.Annals of dermatology · 2015Article
- Hepatitis C, innate immunity and alcohol: friends or foes?Biomolecules · 2015Review
- Signal transducer and activator of transcription 5b (Stat5b) serine 193 is a novel cytokine-induced phospho-regulatory site that is constitutively activated in primary hematopoietic malignancies.The Journal of biological chemistry · 2012Article
- Bambusae caulis in Liquamen Suppresses the Expression of Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine in Human Keratinocytes due to Antioxidant Effect.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Activation of mitogen-activated protein kinases by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) plays an important role in macrophage stimulation.Biochemical pharmacology · 2011Article
- Involvement of ERK and JNK pathways in IFN-γ-induced B7-DC expression on tumor cells.Journal of cancer research and clinical oncology · 2011Article
- Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon-gamma in HaCaT cells, a human keratinocyte cell line.British journal of pharmacology · 2009Article
- Acute alcohol intake induces SOCS1 and SOCS3 and inhibits cytokine-induced STAT1 and STAT3 signaling in human monocytes.Alcoholism, clinical and experimental research · 2008Article
- Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis.Gastroenterology · 2008Article
- Implication of altered proteasome function in alcoholic liver injury.World journal of gastroenterology · 2007Review
- Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases.Journal of virology · 2007Article
- Inhibition of IFN-alpha signaling by a PKC- and protein tyrosine phosphatase SHP-2-dependent pathway.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Enhanced human beta-defensin-2 (hBD-2) expression by corticosteroids is independent of NF-kappaB in colonic epithelial cells (CaCo2).Digestive diseases and sciences · 2005Article
- Intestinal Na+-K+-ATPase activity and molecular events downstream of interferon-gamma receptor stimulation.British journal of pharmacology · 2004Article
- STAT1 deficiency unexpectedly and markedly exacerbates the pathophysiological actions of IFN-alpha in the central nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Cross-talk between interleukin 1beta (IL-1beta) and IL-6 signalling pathways: IL-1beta selectively inhibits IL-6-activated signal transducer and activator of transcription factor 1 (STAT1) by a proteasome-dependent mechanism.The Biochemical journal · 2000Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Interferons (IFNs) have been used in the treatment of viral hepatitis. However, their effectiveness is much reduced (<10%) in alcoholics. The mechanism underlying this resistance remains unknown. Here, we report that IFN-alpha/beta and IFN-gamma rapidly activate the JAK-STAT1 (Janus kinase-signal transducer and activator transcription factor 1) and p42/44 mitogen-activated protein kinase (p42/44 MAPK) in freshly isolated rat hepatocytes. Treatment of hepatocytes with 25-100 mM ethanol for 30 min inhibited IFN-beta- or IFN-gamma-induced STAT1 activation and tyrosine phosphorylation. The inhibitory effect of ethanol was not reversed by pretreatment with either sodium vanadate, a non-selective tyrosine phosphatase inhibitor, or with MG132, a specific proteasome inhibitor. This suggests that protein tyrosine phosphatases or the ubiquitin-proteasome pathway are not involved in the inhibitory action of ethanol. In contrast with the JAK-STAT signalling pathway, acute ethanol exposure significantly potentiated IFN-beta or IFN-gamma-induced activation of p42/44 MAPK, and caused marked activation of protein kinase C (PKC). Inhibition of PKC partially antagonized ethanol attenuation of IFN-induced STAT1 activation, suggesting that PKC may be involved. Taken together, these findings suggest that the ability of biologically relevant concentrations of ethanol (less than 100 mM) to markedly inhibit IFN-activated STAT1 is one of the cellular mechanisms responsible for the observed resistance of IFN therapy in alcoholics.
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